The Yarlung Zangbo River, one of the largest rivers on the Tibetan Plateau, is a hotspot for biodiversity conservation efforts. Schizothorax curvilabiatus is mainly distributed in the waters of the lower trunk and tributaries of the Yarlung Zangbo River, and it is a representative fish of the lower basin. Recently, geological disasters and human activities have caused severe damage to the habitat of the Schizothorax curvilabiatus, leading to a decline in its resources. Consequently, conducting relevant studies to protect the germplasm resources of Schizothorax curvilabiatus is urgently required. In this study, SLAF-seq was used to develop SNPs. Genetic diversity was calculated using a script provided by Beijing Biomarker Technologies Co., Ltd; paired F_ST values between populations were calculated in Stacks; linkage disequilibrium analysis was performed by Plink; phylogenetic analysis, Admixture population structure analysis, and principal component analysis were used to classify the genetic structure of Artemia; and the TreeMix (v.1.13) software was used to calculate the level of gene flow in the populations. A large number of SNPs were identified in Schizothorax curvilabiatus populations. Overall, the genetic diversity of Schizothorax curvilabiatus was small, with MTXG having the highest genetic diversity. Recent geological events, such as weir collapses and earthquakes, have significantly impacted stock levels. Overfishing and biological invasions have also impacted stock levels. Human activities such as engineering construction and sand mining have altered the localized aquatic ecosystem of the river and reduced the population size of Schizothorax curvilabiatus, thus leading to an overall low genetic diversity of the Schizothorax curvilabiatus in the lower reaches of the Yarlung Zangbo River. Schizothorax curvilabiatus populations showed a low to moderate degree of genetic differentiation. The lower reaches of the Yarlung Zangbo River are characterized by considerable differences in elevation, which may act as a barrier to geographic dispersal and promote differentiation among populations of the Schizothorax curvilabiatus. Unexpectedly, MTLD and MTXR were the furthest apart but had the smallest FST within the Motuo population. Excluding the absence of gene flow and common ancestry between the two populations, we hypothesized that this was due to the local effect of genetic drift, which led to the convergence of genetic structure between the two populations and minimized FST. The LD results indicated that the Motuo populations were subjected to greater natural positive selection, and their ability to adapt to the environment was stronger, while the Palong and Chayu populations were subjected to relatively less natural positive selection. The results of the phylogenetic tree, Admixture, and principal component analysis showed that the Schizothorax curvilabiatus in the lower reaches of the Yarlung Zangbo River belong to the same taxon. TreeMix results showed that the optimal number of gene flow was two, both occurring in the Mutuo populations. Geological disasters have decreased the resources available to Schizothorax curvilabiatus, resulting in smaller populations. Additionally, Schizothorax curvilabiatus migrate over long distances and have limited movement patterns, which restricts inter-individual gene flow. This study provides a database for the conservation and exploitation of the germplasm resources of the Schizothorax curvilabiatus in the Yajiang River Basin.